Skip to main navigation menu Skip to main content Skip to site footer

Original article

Vol. 148 No. 0304 (2018)

Excellent outcome of direct antiviral treatment for chronic hepatitis C in Switzerland

  • Jacqueline A. Bachofner
  • Piero V. Valli
  • Irina Bergamin
  • Arne Kröger
  • Patrizia Künzler
  • Adriana Baserga
  • Dominique L. Braun
  • Burkhardt Seifert
  • Anja Moncsek
  • Jan Fehr
  • David Semela
  • Lorenzo Magenta
  • Beat Müllhaupt
  • Benedetta Terziroli Beretta-Piccoli
  • Joachim C. Mertens
  • the Swiss Hepatitis C Cohort Study
DOI
https://doi.org/10.4414/smw.2018.14560
Cite this as:
Swiss Med Wkly. 2018;148:w14560
Published
18.01.2018

Summary

BACKGROUND

The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete.

AIMS OF THE STUDY

We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC.

METHODS

We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis.

RESULTS

Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92–96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94–98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87–100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87–97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76–94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations.

CONCLUSION

In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.

References

  1. Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, et al. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013;368(20):1878–87. doi:.https://doi.org/10.1056/NEJMoa1214853
  2. Zeuzem S, Dusheiko GM, Salupere R, Mangia A, Flisiak R, Hyland RH, et al.; VALENCE Investigators. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med. 2014;370(21):1993–2001. doi:.https://doi.org/10.1056/NEJMoa1316145
  3. Lawitz E, Sulkowski MS, Ghalib R, Rodriguez-Torres M, Younossi ZM, Corregidor A, et al. Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study. Lancet. 2014;384(9956):1756–65. doi:.https://doi.org/10.1016/S0140-6736(14)61036-9
  4. European Association for Study of Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J Hepatol. 2015;63(1):199–236. doi:.https://doi.org/10.1016/j.jhep.2015.03.025
  5. AASLD/IDSA HCV Guidance Panel. Hepatitis C guidance: AASLD-IDSA recommendations for testing, managing, and treating adults infected with hepatitis C virus. Hepatology. 2015;62(3):932–54. doi:.https://doi.org/10.1002/hep.27950
  6. Butt AA, Yan P, Shaikh OS, Freiberg MS, Lo Re V, 3rd, Justice AC, et al.; ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans) Study Team. Virologic response and haematologic toxicity of boceprevir- and telaprevir-containing regimens in actual clinical settings. J Viral Hepat. 2015;22(9):691–700. doi:.https://doi.org/10.1111/jvh.12375
  7. Backus LI, Belperio PS, Shahoumian TA, Cheung R, Mole LA. Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large U.S. cohort. Aliment Pharmacol Ther. 2014;39(1):93–103. doi:.https://doi.org/10.1111/apt.12546
  8. Conti F, Brillanti S, Buonfiglioli F, Vukotic R, Morelli MC, Lalanne C, et al. Safety and efficacy of direct acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older. J Viral Hepat. 2017;24(6):454–63.
  9. Milazzo L, Lai A, Calvi E, Ronzi P, Micheli V, Binda F, et al. Direct-acting antivirals in hepatitis C virus (HCV)-infected and HCV/HIV-coinfected patients: real-life safety and efficacy. HIV Med. 2017;18(4):284–91.
  10. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP ; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147(8):573–7. doi:.https://doi.org/10.7326/0003-4819-147-8-200710160-00010
  11. Prasad L, Spicher VM, Zwahlen M, Rickenbach M, Helbling B, Negro F ; Swiss Hepatitis C Cohort Study Group. Cohort Profile: the Swiss Hepatitis C Cohort Study (SCCS). Int J Epidemiol. 2007;36(4):731–7. doi:.https://doi.org/10.1093/ije/dym096
  12. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48(5):835–47. doi:.https://doi.org/10.1016/j.jhep.2008.02.008
  13. Parczewski M, Leszczyszyn-Pynka M, Urbańska A. Differences in the integrase and reverse transcriptase transmitted resistance patterns in Northern Poland. Infect Genet Evol. 2017;49:122–9. doi:.https://doi.org/10.1016/j.meegid.2016.12.019
  14. Peres-da-Silva A, Brandão-Mello CE, Lampe E. Prevalence of sofosbuvir resistance-associated variants in Brazilian and worldwide NS5B sequences of genotype-1 HCV. Antivir Ther. 2017;22(5):447–51. doi:.https://doi.org/10.3851/IMP3131
  15. Ogawa E, Furusyo N, Nomura H, Dohmen K, Higashi N, Takahashi K, et al. NS5A resistance-associated variants undermine the effectiveness of ledipasvir and sofosbuvir for cirrhotic patients infected with HCV genotype 1b. J Gastroenterol. 2017;52(7):845–54.
  16. Andreone P, Colombo MG, Enejosa JV, Koksal I, Ferenci P, Maieron A, et al. ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection. Gastroenterology. 2014;147(2):359–365.e1. doi:.https://doi.org/10.1053/j.gastro.2014.04.045
  17. Belli LS, Berenguer M, Cortesi PA, Strazzabosco M, Rockenschaub SR, Martini S, et al.; European Liver and Intestine Association (ELITA). Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study. J Hepatol. 2016;65(3):524–31. doi:.https://doi.org/10.1016/j.jhep.2016.05.010
  18. d’Arminio Monforte A, Cozzi-Lepri A, Ceccherini-Silberstein F, De Luca A, Lo Caputo S, Castagna A, et al.; Icona Foundation and HepaIcona Study Group. Access and response to direct antiviral agents (DAA) in HIV-HCV co-infected patients in Italy: Data from the Icona cohort. PLoS One. 2017;12(5):e0177402. doi:.https://doi.org/10.1371/journal.pone.0177402
  19. Bielen R, Moreno C, Van Vlierberghe H, Bourgeois S, Mulkay JP, Vanwolleghem T, et al. Belgian experience with direct acting antivirals in people who inject drugs. Drug Alcohol Depend. 2017;177:214–20. doi:.https://doi.org/10.1016/j.drugalcdep.2017.04.003
  20. Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, et al.; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370(20):1889–98. doi:.https://doi.org/10.1056/NEJMoa1402454
  21. Foster GR, Afdhal N, Roberts SK, Bräu N, Gane EJ, Pianko S, et al.; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015;373(27):2608–17. doi:.https://doi.org/10.1056/NEJMoa1512612
  22. Kim DY, Han KH, Jun B, Kim TH, Park S, Ward T, et al. Estimating the Cost-Effectiveness of One-Time Screening and Treatment for Hepatitis C in Korea. PLoS One. 2017;12(1):e0167770. doi:.https://doi.org/10.1371/journal.pone.0167770
  23. Ayoub HH, Abu-Raddad LJ. Impact of treatment on hepatitis C virus transmission and incidence in Egypt: A case for treatment as prevention. J Viral Hepat. 2017;24(6):486–95.
  24. Ward T, Gordon J, Bennett H, Webster S, Sugrue D, Jones B, et al. Tackling the burden of the hepatitis C virus in the UK: characterizing and assessing the clinical and economic consequences. Public Health. 2016;141:42–51. doi:.https://doi.org/10.1016/j.puhe.2016.08.002
  25. Bach TA, Zaiken K. Real-World Drug Costs of Treating Hepatitis C Genotypes 1-4 with Direct-Acting Antivirals: Initiating Treatment at Fibrosis 0-2 and 3-4. J Manag Care Spec Pharm. 2016;22(12):1437–45. doi:.https://doi.org/10.18553/jmcp.2016.22.12.1437
  26. Gentile I, Maraolo AE, Niola M, Graziano V, Borgia G, Paternoster M. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma. Expert Rev Gastroenterol Hepatol. 2016;10(11):1227–34. doi:.https://doi.org/10.1080/17474124.2016.1234375
  27. Bachofner JA, Valli PV, Kroger A, Bergamin I, Kunzler P, Baserga A, et al. Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index. Liver Int. 2017;37(3):369–76.
  28. Reddy KR, Pol S, Thuluvath PJ, Kumada H, Toyota J, Chayama K, et al. Long-term follow-up of clinical trial patients treated for chronic HCV infection with daclatasvir-based regimens. Liver Int. 2017 Sep 21 [Epub ahead of print] doi:.https://doi.org/10.1111/liv.13596

Most read articles by the same author(s)

1 2 3 > >>